Selective organ cooling apparatus

ABSTRACT

An endovascular heat transfer device which can have a smooth exterior surface, or a surface with ridges and grooves. The device can have a plurality of elongated, articulated segments, with each having such a surface. A flexible joint connects adjacent elongated, articulated segments. The flexible joints can be bellows or flexible tubes. An inner lumen is disposed within the heat transfer segments. The inner lumen is capable of transporting a pressurized working fluid to a distal end of the heat transfer element.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation patent application of co-pending U.S. patentapplication Ser. No. 10/796,906, filed on Mar. 8, 2004, and entitled“Selective Organ Cooling Apparatus and Method”; which is a continuationpatent application of U.S. patent application Ser. No. 10/161,107, filedon May 30, 2002, and entitled “Selective Organ Cooling Apparatus andMethod”; which is a continuation patent application of co-pending U.S.patent application Ser. No. 09/607,799, filed on Jun. 30, 2000, andentitled “Selective Organ Cooling Apparatus and Method”; which is acontinuation-in-part patent application of co-pending U.S. patentapplication Ser. No. 09/570,075, filed on May 12, 2000, and entitled“Selective Organ Cooling Apparatus and Method”; a continuation-in-partpatent application of U.S. patent application Ser. No. 09/215,041, filedon Dec. 16, 1998, and entitled “Articulation Device for Selective OrganCooling Apparatus”, now U.S. Pat. No. 6,254,626; a continuation-in-partpatent application of U.S. patent application Ser. No. 09/103,342, filedon Jun. 23, 1998, and entitled “Selective Organ Cooling Catheter andMethod of Using the Same”, now U.S. Pat. No. 6,096,068; acontinuation-in-part patent application of U.S. patent application Ser.No. 09/052,545, filed on Mar. 31, 1998, and entitled “Circulating FluidHypothermia Method and Apparatus”, now U.S. Pat. No. 6,231,595; and acontinuation-in-part patent application of U.S. patent application Ser.No. 09/047,012, filed on Mar. 24, 1998, and entitled “Selective OrganHypothermia Method and Apparatus”, now U.S. Pat. No. 5,957,963; and acontinuation-in-part patent application of U.S. patent application Ser.No. 09/012,287, filed on Jan. 23, 1998, and entitled “Selective OrganHypothermia Method and Apparatus”, now U.S. Pat. No. 6,051,019. Thedisclosures of these parent applications are hereby incorporated hereinby reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to the modification and controlof the temperature of a selected body organ. More particularly, theinvention relates to a method and intravascular apparatus forcontrolling organ temperature.

2. Background Art

Organs in the human body, such as the brain, kidney and heart, aremaintained at a constant temperature of approximately 37° C. Hypothermiacan be clinically defined as a core body temperature of 35° C. or less.Hypothermia is sometimes characterized further according to itsseverity. A body core temperature in the range of 33° C. to 35° C. isdescribed as mild hypothermia. A body temperature of 28° C. to 32° C. isdescribed as moderate hypothermia. A body core temperature in the rangeof 24° C. to 28° C. is described as severe hypothermia.

Hypothermia is uniquely effective in reducing brain injury caused by avariety of neurological insults and may eventually play an importantrole in emergency brain resuscitation. Experimental evidence hasdemonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

Cerebral hypothermia has traditionally been accomplished through wholebody cooling to create a condition of total body hypothermia in therange of 20° C. to 30° C. However, the use of total body hypothermiarisks certain deleterious systematic vascular effects. For example,total body hypothermia may cause severe derangement of thecardiovascular system, including low cardiac output, elevated systematicresistance, and ventricular fibrillation. Other side effects includerenal failure, disseminated intravascular coagulation, and electrolytedisturbances. In addition to the undesirable side effects, total bodyhypothermia is difficult to administer.

Catheters have been developed which are inserted into the bloodstream ofthe patient in order to induce total body hypothermia. For example, U.S.Pat. No. 3,425,419 to Dato describes a method and apparatus of loweringand raising the temperature of the human body. Dato induces moderatehypothermia in a patient using a metallic catheter. The metalliccatheter has an inner passageway through which a fluid, such as water,can be circulated. The catheter is inserted through the femoral vein andthen through the inferior vena cava as far as the right atrium and thesuperior vena cava. The Dato catheter has an elongated cylindrical shapeand is constructed from stainless steel. By way of example, Datosuggests the use of a catheter approximately 70 cm in length andapproximately 6 mm in diameter. However, use of the Dato deviceimplicates the negative effects of total body hypothermia describedabove.

Due to the problems associated with total body hypothermia, attemptshave been made to provide more selective cooling. For example, coolinghelmets or head gear have been used in an attempt to cool only the headrather than the patient's entire body. However, such methods rely onconductive heat transfer through the skull and into the brain. Onedrawback of using conductive heat transfer is that the process ofreducing the temperature of the brain is prolonged. Also, it isdifficult to precisely control the temperature of the brain when usingconduction due to the temperature gradient that must be establishedexternally in order to sufficiently lower the internal temperature. Inaddition, when using conduction to cool the brain, the face of thepatient is also subjected to severe hypothermia, increasing discomfortand the likelihood of negative side effects. It is known that profoundcooling of the face can cause similar cardiovascular side effects astotal body cooling. From a practical standpoint, such devices arecumbersome and may make continued treatment of the patient difficult orimpossible.

Selected organ hypothermia has been accomplished using extracorporealperfusion, as detailed by Arthur E. Schwartz, M. D. et al., in IsolatedCerebral Hypothermia by Single Carotid Artery Perfusion ofExtracorporeally Cooled Blood in Baboons, which appeared in Vol. 39, No.3, NEUROSURGERY 577 (September, 1996). In this study, blood wascontinually withdrawn from baboons through the femoral artery. The bloodwas cooled by a water bath and then infused through a common carotidartery with its external branches occluded. Using this method, normalheart rhythm, systemic arterial blood pressure and arterial blood gasvalues were maintained during the hypothermia. This study showed thatthe brain could be selectively cooled to temperatures of 20° C. withoutreducing the temperature of the entire body. However, externalcirculation of blood is not a practical approach for treating humansbecause the risk of infection, need for anticoagulation, and risk ofbleeding is too great. Further, this method requires cannulation of twovessels making it more cumbersome to perform particularly in emergencysettings. Even more, percutaneous cannulation of the carotid artery isdifficult and potentially fatal due to the associated arterial walltrauma. Finally, this method would be ineffective to cool other organs,such as the kidneys, because the feeding arteries cannot be directlycannulated percutaneously.

Selective organ hypothermia has also been attempted by perfusion of acold solution such as saline or perfluorocarbons. This process iscommonly used to protect the heart during heart surgery and is referredto as cardioplegia. Perfusion of a cold solution has a number ofdrawbacks, including a limited time of administration due to excessivevolume accumulation, cost, and inconvenience of maintaining theperfusate and lack of effectiveness due to the temperature dilution fromthe blood. Temperature dilution by the blood is a particular problem inhigh blood flow organs such as the brain.

Therefore, a practical method and apparatus which modifies and controlsthe temperature of a selected organ satisfies a long-felt need.

BRIEF SUMMARY OF THE INVENTION

The apparatus of the present invention can, by way of example only,include a heat transfer element which comprises first and secondelongated, articulated segments, each segment can have either aturbulence-inducing or mixing-inducing exterior surface or a smoothexterior surface. A flexible joint can connect the first and secondelongated segments. An inner coaxial lumen may be disposed within thefirst and second elongated segments and is capable of transporting apressurized working fluid to a distal end of the first elongatedsegment. In addition, the first and second elongated segments may have aturbulence-inducing or mixing-inducing interior surface for inducingturbulence or mixing within the pressurized working fluid. Theturbulence-inducing or mixing-inducing exterior surface may be adaptedto induce turbulence or mixing within a free stream of blood flow whenplaced within an artery. The turbulence-inducing exterior surface may beadapted to induce a turbulence intensity greater than 0.05 within a freestream blood flow. In one embodiment, the flexible joint comprises abellows section which also allows for axial compression of the heattransfer element. In another embodiment, the flexible joint comprises astraight, flexible tube as disclosed in U.S. patent application Ser. No.09/215,041, filed on Dec. 16, 1998, and entitled “Articulation Devicefor Selective Organ Cooling Apparatus”, the disclosure of which isentirely incorporated herein by reference.

In one embodiment, the turbulence-inducing or mixing-inducing exteriorsurfaces of the heat transfer element comprise one or more alternatingridges and grooves. The ridges and grooves can be aligned longitudinallyalong the heat transfer element, or they can be arranged helicallyaround the heat transfer element. Where straight ridges and grooves areused, adjacent segments can have their ridges angularly offset from eachother, to increase turbulence or mixing. Similarly, where helical ridgesare used, adjacent segments of the heat transfer element can beoppositely spiraled, to increase turbulence or mixing. For instance, thefirst elongated heat transfer segment may comprise one or more helicalridges having a counter-clockwise twist, while the second elongated heattransfer segment comprises one or more helical ridges having a clockwisetwist. Alternatively, of course, the first elongated heat transfersegment may comprise one or more clockwise helical ridges, and thesecond elongated heat transfer segment may comprise one or morecounter-clockwise helical ridges. The first and second elongated,articulated segments may be formed from highly conductive materials,such as a metal, or a polymer doped or loaded with particles orfilaments of a conductive material. Where the surface has sufficientlypronounced features such as ridges, the enhanced surface area alone mayprovide sufficient heat transfer, without a need for angular offsets, oropposite spirals, to induce turbulence or mixing.

In another embodiment, the turbulence-inducing or mixing-inducingexterior surface of the heat transfer element is adapted to induceturbulence or mixing throughout the duration of each pulse of apulsatile blood flow when placed within an artery. In still anotherembodiment, the turbulence-inducing or mixing-inducing exterior surfaceof the heat transfer element is adapted to induce turbulence or mixingduring at least 20% of the period of each cardiac cycle when placedwithin an artery.

In yet another embodiment, the exterior surface of the heat transferelement may be an entirely smooth surface, such as a right circularcylinder. The segments of the heat transfer element can have a smoothexterior surface, where the surface area is large enough to providesufficient heat transfer. Here again, the articulated segments may beformed from highly conductive materials, such as a metal, or a polymerdoped or loaded with particles or filaments of a conductive material.

The heat transfer device may also have a coaxial supply catheter with aninner catheter lumen coupled to the inner coaxial lumen within the firstand second elongated heat transfer segments. A working fluid supplyconfigured to dispense the pressurized working fluid may be coupled tothe inner catheter lumen. The working fluid supply may be configured toproduce the pressurized working fluid at a temperature of about 0° C.and at a pressure below about 5 atmospheres of pressure.

In yet another alternative embodiment, the heat transfer device may havethree or more elongated, articulated, heat transfer segments having aturbulence-inducing, mixing-inducing, or smooth exterior surface, withadditional flexible joints connecting the additional elongated heattransfer segments. In one such embodiment, by way of example, the firstand third elongated heat transfer segments may comprise clockwisehelical ridges, and the second elongated heat transfer segment maycomprise one or more counter-clockwise helical ridges. Alternatively, ofcourse, the first and third elongated heat transfer segments maycomprise counter-clockwise helical ridges, and the second elongated heattransfer segment may comprise one or more clockwise helical ridges. Asstill another alternative, in the use of longitudinal ridges, the secondelongated heat transfer segment may have longitudinal ridges offset by aradial angle from the longitudinal ridges on the first segment, and thethird heat transfer segment may have longitudinal ridges offset by aradial angle from the longitudinal ridges on the second segment. As yetanother alternative, of course, each elongated heat transfer segment canbe a smooth right circular cylinder. Further, a mixture of these typesof elongated heat transfer segments can be used on a heat transferdevice.

The turbulence-inducing, mixing-inducing, or smooth exterior surface ofthe heat transfer element may optionally include a surface coating ortreatment to inhibit clot formation. One variation of the heat transferelement comprises a stent coupled to a distal end of the first elongatedheat transfer segment.

The present invention also envisions a method of treating the brainwhich comprises the steps of inserting a flexible, conductive heattransfer element into a carotid artery from a distal location, andcirculating a working fluid through the flexible, conductive heattransfer element in order to selectively modify the temperature of thebrain without significantly modifying the temperature of the entirebody. The flexible, conductive heat transfer element preferably absorbsmore than about 25, 50 or 75 Watts of heat.

The method may also comprise the step of inducing turbulence or mixingwithin the free stream blood flow within the carotid artery. In oneembodiment, the method includes the step of inducing blood turbulencewith a turbulence intensity greater than about 0.05 within the carotidartery. In another embodiment, the method includes the step of inducingblood turbulence or mixing throughout the duration of the period of thecardiac cycle within the carotid artery. In yet another embodiment, themethod comprises the step of inducing blood turbulence or mixingthroughout the period of the cardiac cycle within the carotid artery orduring greater than about 20% of the period of the cardiac cycle withinthe carotid artery. The step of circulating may comprise the step ofinducing turbulent flow or mixing of the working fluid through theflexible, conductive heat transfer element. The pressure of the workingfluid may be maintained below about 5 atmospheres of pressure.

The present invention also envisions a method for selectively cooling anorgan in the body of a patient which comprises the steps of introducinga catheter, with a heat transfer element, into a blood vessel supplyingthe organ, the catheter having a diameter of about 4 mm or less,inducing free stream turbulence or mixing in blood flowing over the heattransfer element, and cooling the heat transfer element to remove heatfrom the blood to cool the organ without substantially cooling theentire body. In one embodiment, the cooling step removes at least about75 Watts of heat from the blood. In another embodiment, the cooling stepremoves at least about 100 Watts of heat from the blood. The organ beingcooled may be the human brain.

The step of inducing free stream turbulence may induce a turbulenceintensity greater than about 0.05 within the blood vessel. The step ofinducing free stream turbulence may induce turbulence throughout theduration of each pulse of blood flow. The step of inducing free streamturbulence may induce turbulence for at least about 20% of the durationof each pulse of blood flow.

In one embodiment, the catheter has a flexible metal, or doped polymer,tip and the cooling step occurs at the tip. The tip may have smooth,turbulence-inducing, or mixing-inducing elongated heat transfer segmentsseparated by bellows sections. The turbulence-inducing ormixing-inducing segments may comprise longitudinal or helical ridgeswhich are configured to have a depth which is greater than a thicknessof a boundary layer of blood which develops within the blood vessel. Inanother embodiment, the catheter has a tip at which the cooling stepoccurs and the tip has turbulence-inducing or mixing-inducing elongatedheat transfer segments that alternately spiral bias the surroundingblood flow in clockwise and counterclockwise directions.

The cooling step may comprise the step of circulating a working fluid inthrough an inner lumen in the catheter and out through an outer, coaxiallumen. In one embodiment, the working fluid remains a liquid throughoutthe cycle. The working fluid may be aqueous.

The present invention also envisions a cooling catheter comprising acatheter shaft having first and second lumens therein. The coolingcatheter also comprises a cooling tip adapted to transfer heat to orfrom a working fluid circulated in through the first lumen and outthrough the second lumen, and either a smooth exterior surface orturbulence-inducing or mixing-inducing structures on the cooling tipcapable of inducing free stream turbulence or mixing when the tip isinserted into a blood vessel. The turbulence-inducing structures mayinduce a turbulence intensity of at least about 0.05. The cooling tipmay be adapted to induce turbulence or mixing within the working fluid.The catheter is capable of removing at least about 25 Watts of heat froman organ when inserted into a vessel supplying that organ, while coolingthe tip with a working fluid that remains a liquid in the catheter.Alternatively, the catheter is capable of removing at least about 50 or75 Watts of heat from an organ when inserted into a vessel supplyingthat organ, while cooling the tip with an aqueous working fluid. In oneembodiment, in use, the tip has a diameter of about 4 mm or less.Optionally, the turbulence-inducing or mixing-inducing surfaces on theheat transfer segments comprise longitudinal or helical ridges whichhave a depth sufficient to disrupt the free stream blood flow in theblood vessel. Alternatively, the turbulence-inducing or mixing-inducingsurfaces may comprise staggered protrusions from the outer surfaces ofthe heat transfer segments, which have a height sufficient to disruptthe free stream flow of blood within the blood vessel.

In another embodiment, a cooling catheter may comprise a catheter shafthaving first and second lumens therein, a cooling tip adapted totransfer heat to or from a working fluid circulated in through the firstlumen and out through the second lumen, and either a smooth exteriorsurface or turbulence-inducing or mixing-inducing structures on thecooling tip capable of inducing turbulence or mixing when the tip isinserted into a blood vessel. Alternatively, a cooling catheter maycomprise a catheter shaft having first and second lumens therein, acooling tip adapted to transfer heat to or from a working fluidcirculated in through the first lumen and out through the second lumen,and structures on the cooling tip capable of inducing free streamturbulence or mixing when the tip is inserted into a blood vessel. Inanother embodiment, a cooling catheter may comprise a catheter shafthaving first and second lumens therein, a cooling tip adapted totransfer heat to or from a working fluid circulated in through the firstlumen and out through the second lumen, and turbulence-inducingstructures on the cooling tip capable of inducing turbulence with anintensity greater than about 0.05 when the tip is inserted into a bloodvessel.

The novel features of this invention, as well as the invention itself,will be best understood from the attached drawings, taken along with thefollowing description, in which similar reference characters refer tosimilar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a graph illustrating the velocity of steady state turbulentflow as a function of time;

FIG. 2A is a graph showing the velocity of the blood flow within anartery as a function of time;

FIG. 2B is a graph illustrating the velocity of steady state turbulentflow under pulsatile conditions as a function of time, similar toarterial blood flow;

FIG. 2C is an elevation view of a turbulence inducing heat transferelement within an artery;

FIG. 3A is a velocity profile diagram showing a typical steady statePoiseuillean flow driven by a constant pressure gradient;

FIG. 3B is a velocity profile diagram showing blood flow velocity withinan artery, averaged over the duration of the cardiac pulse;

FIG. 3C is a velocity profile diagram showing blood flow velocity withinan artery, averaged over the duration of the cardiac pulse, afterinsertion of a smooth heat transfer element within the artery;

FIG. 4 is an elevation view of one embodiment of a heat transfer elementaccording to the invention, with alternating helices;

FIG. 5 is longitudinal section view of the heat transfer element of FIG.4;

FIG. 6 is a transverse section view of the heat transfer element of FIG.4;

FIG. 7 is a perspective view of the heat transfer element of FIG. 4 inuse within a blood vessel;

FIG. 8 is a cut-away perspective view of a second embodiment of a heattransfer element according to the invention, with protrusions on thesurface;

FIG. 9 is a transverse section view of the heat transfer element of FIG.8;

FIG. 10 is a schematic representation of the invention being used in oneembodiment to cool the brain of a patient;

FIG. 11 is a perspective view of a third embodiment of a heat transferelement according to the invention, with aligned longitudinal ridges onadjacent segments;

FIG. 12 is a perspective view of a fourth embodiment of a heat transferelement according to the invention, with offset longitudinal ridges onadjacent segments; and

FIG. 13 is a transverse section view of the heat transfer element ofFIG. 11 or FIG. 12.

DETAILED DESCRIPTION OF THE INVENTION

In order to intravascularly regulate the temperature of a selectedorgan, a heat transfer element may be placed in the feeding artery ofthe organ to absorb or deliver the heat from or to the blood flowinginto the organ. The transfer of heat may cause either a cooling or aheating of the selected organ. The heat transfer element must be smallenough to fit within the feeding artery while still allowing asufficient blood flow to reach the organ in order to avoid ischemicorgan damage. A heat transfer element which selectively cools an organshould be capable of providing the necessary heat transfer rate toproduce the desired cooling or heating effect within the organ. Byplacing the heat transfer element within the feeding artery of an organ,the temperature of an organ can be controlled without significantlyaffecting the remaining parts of the body. These points can beillustrated by using brain cooling as an example.

The common carotid artery supplies blood to the head and brain. Theinternal carotid artery branches off of the common carotid to directlysupply blood to the brain. To selectively cool the brain, the heattransfer element is placed into the common carotid artery, or both thecommon carotid artery and the internal carotid artery. The internaldiameter of the common carotid artery ranges from 6 to 8 mm and thelength ranges from 80 to 120 mm. Thus, the heat transfer elementresiding in one of these arteries cannot be much larger than 4 mm indiameter in order to avoid occluding the vessel.

It is important that the heat transfer element be flexible in order tobe placed within the small feeding artery of an organ. Feeding arteries,like the carotid artery, branch off the aorta at various levels.Subsidiary arteries continue to branch off the initial branches. Forexample, the internal carotid artery is a small diameter artery thatbranches off of the common carotid artery near the angle of the jaw.Because the heat transfer element is typically inserted into aperipheral artery, such as the femoral artery, and accesses the feedingartery by initially passing though a series of one or more of thesebranches, the flexibility of the heat transfer element is an importantcharacteristic of the heat transfer element. Further, the heat transferelement is ideally constructed from a highly thermally conductivematerial such as metal, or a metal-doped polymer, in order to facilitateheat transfer. The use of a highly thermally conductive materialincreases the heat transfer rate for a given temperature differentialbetween the coolant within the heat transfer element and the blood. Thisfacilitates the use of a higher temperature coolant within the heattransfer element, allowing safer coolants, such as water, to be used.Highly thermally conductive materials, such as metals, tend to be rigid.Therefore, the design of the heat transfer element should facilitateflexibility in an inherently inflexible material. Alternatively, theheat transfer element can be constructed of a flexible polymer doped orloaded with particles or filaments of a conductive material, such as ametal.

In order to obtain the benefits of hypothermia described above, it isdesirable to reduce the temperature of the blood flowing to the brain tobetween 30° C. and 32° C. Given that a typical brain has a blood flowrate through each carotid artery (right and left) of approximately250-375 cubic centimeters per minute, the heat transfer element shouldabsorb 75-175 Watts of heat when placed in one of the carotid arteries,in order to induce the desired cooling effect. It should be noted thatsmaller organs may have less blood flow in the supply artery and mayrequire less heat transfer, such as 25 Watts.

When a heat transfer element is inserted coaxially into an artery, theprimary mechanism of heat transfer between the surface of the heattransfer element and the blood is forced convection. Convection reliesupon the movement of fluid to transfer heat. Forced convection resultswhen an external force causes motion within the fluid. In the case ofarterial flow, the beating heart causes the motion of the blood aroundthe heat transfer element.

The magnitude of the heat transfer rate is proportional to the surfacearea of the heat transfer element, the temperature differential, and theheat transfer coefficient of the heat transfer element.

As noted above, the receiving artery into which the heat transferelement is placed has a limited diameter and length. Thus, surface areaof the heat transfer element must be limited, to avoid significantobstruction of the artery, and to allow the heat transfer element toeasily pass through the vascular system. For placement within theinternal and common carotid artery, the cross sectional diameter of theheat transfer element is limited to about 4 mm, and its length islimited to approximately 10 cm.

The temperature differential can be increased by decreasing the surfacetemperature of the heat transfer element. However, the minimum allowablesurface temperature is limited by the characteristics of blood. Bloodfreezes at approximately 0° C. When the blood approaches freezing, iceemboli may form in the blood which may lodge downstream, causing seriousischemic injury. Furthermore, reducing the temperature of the blood alsoincreases its viscosity, which results in a small decrease in the valueof the convection heat transfer coefficient. In addition, increasedviscosity of the blood may result in an increase in the pressure dropwithin the artery, thus, compromising the flow of blood to the brain.Given the above constraints, it is advantageous to limit the minimumallowable surface temperature of the heat transfer element toapproximately 5° C. This results in a maximum temperature differentialbetween the blood stream and the heat transfer element of approximately32° C.

The mechanisms by which the value of the convection heat transfercoefficient may be increased are complex. A heat transfer element with asmooth exterior surface may be able to provide the desired amount ofheat transfer. However, it is well known that the convection heattransfer coefficient increases with the level of turbulent kineticenergy in the fluid flow. Thus, if flow past a smooth heat transferelement will not transfer sufficient heat, it is advantageous to haveturbulent or otherwise mixed blood flow in contact with the heattransfer element.

FIG. 1 is a graph illustrating steady state turbulent flow. The verticalaxis is the velocity of the flow. The horizontal axis represents time.The average velocity of the turbulent flow is shown by a line 100. Theactual instantaneous velocity of the flow is shown by a curve 102.

Under constant pressure conditions, steady flows in pipes arecharacterized as a balance between viscous stresses and the constantpressure gradient. Such flows are called Poiseuillean. FIG. 3A is avelocity profile diagram showing a typical steady state Poiseuilleanflow driven by a constant pressure gradient. The velocity of the fluidacross the pipe is shown in FIG. 3A by the parabolic curve andcorresponding velocity vectors. The velocity of the fluid in contactwith the wall of the pipe is zero. The boundary layer is the region ofthe flow in contact with the pipe surface in which viscous stresses aredominant. In steady state Poiseuillean flow, the boundary layer developsuntil it includes the whole pipe, i.e., the boundary layer thickness inFIG. 3A is one half of the diameter of the pipe.

Under conditions of Poiseuillean flow, the Reynolds number, the ratio ofinertial forces to viscous forces, can be used to characterize the levelof turbulent kinetic energy existing in the flow. For Poiseuilleanflows, Reynolds numbers must be greater than about 2300 to cause atransition from laminar to turbulent flow. Further, when the Reynoldsnumber is greater than about 2000, the boundary layer is receptive to“tripping”. Tripping is a process by which a small perturbation in theboundary layer can create turbulent conditions. The receptivity of aboundary layer to “tripping” is proportional to the Reynolds number andis nearly zero for Reynolds numbers less than 2000.

In contrast with the steady Poiseuillean flow, the blood flow inarteries is induced by the beating heart and is therefore pulsatile.FIG. 2A is a graph showing the velocity of the blood flow within anartery as a function of time. The beating heart provides pulsatile flowwith an approximate period of 0.5 to 1 second. This is known as theperiod of the cardiac cycle. The horizontal axis in FIG. 2A representstime in seconds and the vertical axis represents the average velocity ofblood in centimeters per second. Although very high velocities arereached at the peak of the pulse, the high velocity occurs for only asmall portion of the cycle. In fact, the velocity of the blood reacheszero in the carotid artery at the end of a pulse and temporarilyreverses.

Because of the relatively short duration of the cardiac pulse, the bloodflow in the arteries does not develop into the classic Poiseuilleanflow. FIG. 3B is a velocity profile diagram showing blood flow velocitywithin an artery averaged over the cardiac pulse. The majority of theflow within the artery has the same velocity. The boundary layer wherethe flow velocity decays from the free stream value to zero is verythin, typically ⅙ to 1/20 of the diameter of the artery, as opposed toone half of the diameter of the artery in the Poiseuillean flowcondition.

As noted above, if the flow in the artery were steady rather thanpulsatile, the transition from laminar to turbulent flow would occurwhen the value of the Reynolds number exceeds about 2,000. However, inthe pulsatile arterial flow, the value of the Reynolds number variesduring the cardiac cycle, just as the flow velocity varies. In pulsatileflows, due to the enhanced stability associated with the acceleration ofthe free stream flow, the critical value of the Reynolds number at whichthe unstable modes of motion grow into turbulence is found to be muchhigher, perhaps as high as 9,000.

The blood flow in the arteries of interest remains laminar over morethan 80% of the cardiac cycle. Referring again to FIG. 2A, the bloodflow is turbulent from approximately time t₁ until time t₂ during asmall portion of the descending systolic flow, which is less than 20% ofthe period of the cardiac cycle. If a heat transfer element is placedinside the artery, heat transfer will be facilitated during this shortinterval. However, to transfer the necessary heat to cool the brainturbulent kinetic energy should be produced in the blood stream andsustained throughout the entire period of the cardiac cycle.

A thin boundary layer has been shown to form during the cardiac cycle.This boundary layer will form over the surface of a smooth heat transferelement. FIG. 3C is a velocity profile diagram showing blood flowvelocity within an artery, averaged over the cardiac pulse, afterinsertion of a smooth heat transfer element within the artery. In FIG.3C, the diameter of the heat transfer element is about one half of thediameter of the artery. Boundary layers develop adjacent to the heattransfer element as well as next to the walls of the artery. Each ofthese boundary layers has approximately the same thickness as theboundary layer which would have developed at the wall of the artery inthe absence of the heat transfer element. The free stream flow region isdeveloped in an annular ring around the heat transfer element. Bloodflow past such a smooth heat transfer element may transfer sufficientheat to accomplish the desired temperature control.

One way to increase the heat transfer rate is to create a turbulentboundary layer on the heat transfer element surface. However, turbulencein the very thin boundary layer will not produce sufficient kineticenergy to produce the necessary heat transfer rate. Therefore, to inducesufficient turbulent kinetic energy to increase the heat transfer ratesufficiently to cool the brain, a stirring mechanism, which abruptlychanges the direction of velocity vectors, should be utilized. This cancreate high levels of turbulence intensity in the free stream, therebysufficiently increasing the heat transfer rate.

This turbulence intensity should ideally be sustained for a significantportion of the cardiac cycle. Further, turbulent kinetic energy shouldideally be created throughout the free stream and not just in theboundary layer. FIG. 2B is a graph illustrating the velocity ofcontinually turbulent flow under pulsatile conditions as a function oftime, which would result in optimal heat transfer in arterial bloodflow. Turbulent velocity fluctuations are seen throughout the cycle asopposed to the short interval of fluctuations seen in FIG. 2A betweentime t, and time t₂. These velocity fluctuations are found within thefree stream. The turbulence intensity shown in FIG. 2B is at least 0.05.In other words, the instantaneous velocity fluctuations deviate from themean velocity by at least 5%. Although, ideally, turbulence or mixing iscreated throughout the entire period of the cardiac cycle, the benefitsof turbulence are also obtained if the turbulence or mixing is sustainedfor only 75%, 50% or even as low as 30% or 20% of the cardiac cycle.

To create the desired level of turbulence intensity or mixing in theblood free stream during the whole cardiac cycle, one embodiment of theinvention uses a modular design. This design creates helical blood flowand produces a high level of mixing in the free stream.

For a swirling flow in a tube in which the azimuthal velocity of thefluid vanishes toward the stationary outer boundary, any non-vanishingazimuthal velocity in the interior of the flow will result in aninstability in which the inner fluid is spontaneously exchanged withfluid near the wall, analogous to Taylor cells in the purely azimuthalflow between a rotating inner cylinder and stationary outer cylinder.This instability results from the lack of any force in opposition to thecentripetal acceleration of the fluid particles moving along helicalpaths, the pressure in the tube being a function only of longitudinalposition. In one embodiment, the device of the present invention impartsan azimuthal velocity to the interior of a developed pipe flow, with thenet result being a continuous exchange of fluid between the core andperimeter of the flow as it moves longitudinally down the pipe. Thisfluid exchange enhances the transport of heat, effectively increasingthe convective heat transfer coefficient over that which would haveobtained in undisturbed pipe flow. This bulk exchange of fluid is notnecessarily turbulent, although turbulence is possible if the inducedazimuthal velocity is sufficiently high.

FIG. 2C is a perspective view of such a turbulence inducing ormixing-inducing heat transfer element within an artery. In thisembodiment, turbulence or mixing is further enhanced by periodicallyforcing abrupt changes in the direction of the helical blood flow.Turbulent or mixed flow would be found at point 114, in the free streamarea. The abrupt changes in flow direction are achieved through the useof a series of two or more heat transfer segments, each comprised of oneor more helical ridges. Ideally, the segments will be close enoughtogether to prevent re-laminarization of the flow in between segments.

The use of periodic abrupt changes in the helical direction of the bloodflow in order to induce strong free stream turbulence or mixing may beillustrated with reference to a common clothes washing machine. Therotor of a washing machine spins initially in one direction causinglaminar flow. When the rotor abruptly reverses direction, significantturbulent kinetic energy is created within the entire wash basin as thechanging currents cause random turbulent mixing motion within theclothes-water slurry.

FIG. 4 is an elevation view of one embodiment of a heat transfer element14 according to the present invention. The heat transfer element 14 iscomprised of a series of elongated, articulated segments or modules 20,22, 24. Three such segments are shown in this embodiment, but two ormore such segments could be used without departing from the spirit ofthe invention. As seen in FIG. 4, a first elongated heat transfersegment 20 is located at the proximal end of the heat transfer element14. A turbulence-inducing or mixing-inducing exterior surface of thesegment 20 comprises four parallel helical ridges 28 with four parallelhelical grooves 26 therebetween. One, two, three, or more parallelhelical ridges 28 could also be used without departing from the spiritof the present invention. In this embodiment, the helical ridges 28 andthe helical grooves 26 of the heat transfer segment 20 have a left handtwist, referred to herein as a counter-clockwise spiral or helicalrotation, as they proceed toward the distal end of the heat transfersegment 20.

The first heat transfer segment 20 is coupled to a second elongated heattransfer segment 22 by a first flexible section such as a bellowssection 25, which provides flexibility and compressibility.Alternatively, the flexible section may be a simple flexible tube, verysimilar to a smooth heat transfer segment as shown in FIG. 3C, butflexible. The second heat transfer segment 22 comprises one or morehelical ridges 32 with one or more helical grooves 30 therebetween. Theridges 32 and grooves 30 have a right hand, or clockwise, twist as theyproceed toward the distal end of the heat transfer segment 22. Thesecond heat transfer segment 22 is coupled to a third elongated heattransfer segment 24 by a second flexible section such as a bellowssection 27 or a flexible tube. The third heat transfer segment 24comprises one or more helical ridges 36 with one or more helical grooves34 therebetween. The helical ridge 36 and the helical groove 34 have aleft hand, or counter-clockwise, twist as they proceed toward the distalend of the heat transfer segment 24. Thus, successive heat transfersegments 20, 22, 24 of the heat transfer element 14 alternate betweenhaving clockwise and counterclockwise helical twists. The actual left orright hand twist of any particular segment is immaterial, as long asadjacent segments have opposite helical twist.

In addition, the rounded contours of the ridges 28, 32, 36 also allowthe heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall. A heat transfer element according to the present inventionmay be comprised of two, three, or more heat transfer segments.

The bellows sections 25, 27 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidwhich is cycled through the heat transfer element 14. The structure ofthe bellows sections 25, 27 allows them to bend, extend and compress,which increases the flexibility of the heat transfer element 14 so thatit is more readily able to navigate through blood vessels. The bellowssections 25, 27 also provide for axial compression of the heat transferelement 14, which can limit the trauma when the distal end of the heattransfer element 14 abuts a blood vessel wall. The bellows sections 25,27 are also able to tolerate cryogenic temperatures without a loss ofperformance, facilitating use of the heat transfer element in lowtemperature ablation of tissue.

As an alternative to a heat transfer element 14 made entirely of a metalor a metal-doped polymer, the exterior surfaces of the heat transferelement 14 can be made from metal, and this metal may comprise very highthermal conductivity materials such as nickel, thereby facilitating heattransfer. Alternatively, other metals such as stainless steel, titanium,aluminum, silver, copper and the like, can be used, with or without anappropriate coating or treatment to enhance biocompatibility or inhibitclot formation. Suitable biocompatible coatings include, e.g., gold,platinum or polymer paralyene. The heat transfer element 14 may bemanufactured by plating a thin layer of metal on a mandrel that has theappropriate pattern. In this way, the heat transfer element 14 may bemanufactured inexpensively in large quantities, which is an importantfeature in a disposable medical device.

Because the heat transfer element 14 may dwell within the blood vesselfor extended periods of time, such as 24-48 hours or even longer, it maybe desirable to treat the surfaces of the heat transfer element 14 toavoid clot formation. In particular, one may wish to treat the bellowssections 25, 27 because stagnation of the blood flow may occur in theconvolutions, thus allowing clots to form and cling to the surface toform a thrombus. One means by which to prevent thrombus formation is tobind an antithrombogenic agent to the surface of the heat transferelement 14. For example, heparin is known to inhibit clot formation andis also known to be useful as a biocoating. Alternatively, the surfacesof the heat transfer element 14 may be bombarded with ions such asnitrogen. Bombardment with nitrogen can harden and smooth the surfaceand, thus prevent adherence of clotting factors to the surface.

FIG. 5 is a longitudinal sectional view of the heat transfer element 14of an embodiment of the invention, taken along line 5-5 in FIG. 4. Someinterior contours are omitted for purposes of clarity. An inner tube 42creates an inner coaxial lumen 42 and an outer coaxial lumen 46 withinthe heat transfer element 14. Once the heat transfer element 14 is inplace in the blood vessel, a working fluid such as saline or otheraqueous solution may be circulated through the heat transfer element 14.Fluid flows up a supply catheter into the inner coaxial lumen 40. At thedistal end of the heat transfer element 14, the working fluid exits theinner coaxial lumen 40 and enters the outer lumen 46. As the workingfluid flows through the outer lumen 46, heat is transferred from theworking fluid to the exterior surface 37 of the heat transfer element14. Because the heat transfer element 14 is constructed from a highconductivity material, the temperature of its exterior surface 37 mayreach very close to the temperature of the working fluid. The tube 42may be formed as an insulating divider to thermally separate the innerlumen 40 from the outer lumen 46. For example, insulation may beachieved by creating longitudinal air channels in the wall of theinsulating tube 42. Alternatively, the insulating tube 42 may beconstructed of a non-thermally conductive material likepolytetrafluoroethylene or some other polymer.

It is important to note that the same mechanisms that govern the heattransfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid whichremains a liquid as the coolant. Other coolants such as freon undergonucleate boiling and create turbulence through a different mechanism.Saline is a safe coolant because it is non-toxic, and leakage of salinedoes not result in a gas embolism, which could occur with the use ofboiling refrigerants. Since turbulence or mixing in the coolant isenhanced by the shape of the interior surface 38 of the heat transferelement 14, the coolant can be delivered to the heat transfer element 14at a warmer temperature and still achieve the necessary heat transferrate. Further, as the working fluid passes through a bellows sectioninto a heat transfer segment, the bellows can create a “jet effect” intothe adjacent heat transfer segment, thereby enhancing interior mixing.

This has a number of beneficial implications in the need for insulationalong the catheter shaft length. Due to the decreased need forinsulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element stiff and cause it topush against the wall of the blood vessel, thereby shielding part of theexterior surface 37 of the heat transfer element 14 from the blood.Because of the increased heat transfer characteristics achieved by thealternating helical ridges 28, 32, 36, the pressure of the working fluidmay be as low as 5 atmospheres, 3 atmospheres, 2 atmospheres or evenless than 1 atmosphere.

FIG. 6 is a transverse sectional view of the heat transfer element 14 ofthe invention, taken at a location denoted by the line 6-6 in FIG. 4.FIG. 6 illustrates a five lobed embodiment, whereas FIG. 4 illustrates afour-lobed embodiment. As mentioned earlier, any number of lobes mightbe used. In FIG. 6, the coaxial construction of the heat transferelement 14 is clearly shown. The inner coaxial lumen 40 is defined bythe insulating coaxial tube 42. The outer lumen 46 is defined by theexterior surface of the insulating coaxial tube 42 and the interiorsurface 38 of the heat transfer element 14. In addition, the helicalridges 32 and helical grooves 30 may be seen in FIG. 6. If desired, thedepth of the grooves, d, can be greater than the boundary layerthickness which would have developed if a cylindrical heat transferelement were introduced. For example, in a heat transfer element 14 witha 4 mm outer diameter, the depth of the invaginations, d, may beapproximately equal to 1 mm if designed for use in the carotid artery.Although FIG. 6 shows four ridges and four grooves, the number of ridgesand grooves may vary. Thus, heat transfer elements with 1, 2, 3, 4, 5,6, 7, 8 or more ridges are specifically contemplated.

FIG. 7 is a perspective view of a heat transfer element 14 in use withina blood vessel, showing only one helical lobe per segment for purposesof clarity. Beginning from the proximal end of the heat transfer element(not shown in FIG. 7), as the blood moves forward during the systolicpulse, the first helical heat transfer segment 20 induces acounter-clockwise rotational inertia to the blood. As the blood reachesthe second segment 22, the rotational direction of the inertia isreversed, causing turbulence or mixing within the blood. Further, as theblood reaches the third segment 24, the rotational direction of theinertia is again reversed. The sudden changes in flow direction activelyreorient and randomize the velocity vectors, thus ensuring turbulence ormixing throughout the bloodstream. During turbulent or mixed flow, thevelocity vectors of the blood become more random and, in some cases,become perpendicular to the axis of the artery. In addition, as thevelocity of the blood within the artery decreases and reverses directionduring the cardiac cycle, additional turbulence or mixing is induced andturbulent motion is sustained throughout the duration of each pulsethrough the same mechanisms described above.

Thus, a large portion of the volume of warm blood in the vessel isactively brought in contact with the heat transfer element 14, where itcan be cooled by direct contact rather than being cooled largely byconduction through adjacent laminar layers of blood. In this embodiment,free stream turbulence or mixing is induced. Where a smooth heattransfer element is not sufficient, in order to create the desired levelof turbulence or mixing in the entire blood stream during the wholecardiac cycle, the heat transfer element 14 creates a turbulenceintensity greater than about 0.05. The turbulence intensity may begreater than 0.05, 0.06, 0.07 or up to 0.10 or 0.20 or greater.

Referring back to FIG. 4, the heat transfer element 14 has been designedto address all of the design criteria discussed above. First, the heattransfer element 14 is flexible and is made of a highly conductivematerial. The flexibility is provided by a segmental distribution offlexible sections such as bellows sections 25, 27 or flexible tubes,which provide an articulating mechanism. Bellows have a known convoluteddesign which provides flexibility. Second, the exterior surface area 37has been increased through the use of helical ridges 28, 32, 36 andhelical grooves 26, 30, 34. The ridges also allow the heat transferelement 14 to maintain a relatively atraumatic profile, therebyminimizing the possibility of damage to the vessel wall. Third, the heattransfer element 14 has been designed to promote turbulent kineticenergy both internally and externally. The modular or segmental designallows the direction of the invaginations to be reversed betweensegments. The alternating helical rotations create an alternating flowthat results in mixing the blood in a manner analogous to the mixingaction created by the rotor of a washing machine that switchesdirections back and forth. This mixing action is intended to promotehigh level turbulent kinetic energy to enhance the heat transfer rate.The alternating helical design also causes beneficial mixing, orturbulent kinetic energy, of the working fluid flowing internally.

FIG. 8 is a cut-away perspective view of a second embodiment of a heattransfer element 50. An external surface 52 of the heat transfer element50 is covered with a series of axially staggered protrusions 54. Thestaggered nature of the outer protrusions 54 is readily seen withreference to FIG. 9 which is a transverse cross-sectional view taken ata location denoted by the line 9-9 in FIG. 8. If desired, the height,d_(p), of the staggered outer protrusions 54 can be greater than thethickness of the boundary layer which would develop if a smooth heattransfer element had been introduced into the blood stream. As the bloodflows along the external surface 52, it collides with one of thestaggered protrusions 54 and a turbulent wake flow is created behind theprotrusion. As the blood divides and swirls along side of the firststaggered protrusion 54, its turbulent wake encounters another staggeredprotrusion 54 within its path preventing the re-lamination of the flowand creating yet more turbulence. In this way, the velocity vectors arerandomized and turbulence or mixing is created not only in the boundarylayer but throughout the free stream. As is the case with the preferredembodiment, this geometry also induces a turbulent or mixing effect onthe internal coolant flow.

A working fluid is circulated up through an inner coaxial lumen 56defined by an insulating coaxial tube 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 60 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside surface of the heat transferelement 50 is similar to the exterior surface 52, in order to induceturbulent or mixing flow of the working fluid. The inner protrusions canbe aligned with the outer protrusions 54, as shown in FIG. 9, or theycan be offset from the outer protrusions 54, as shown in FIG. 8.

The embodiment of FIGS. 8 and 9 may result in a Nusselt number (“Nu”) ofabout 1 to 50. The Nusselt number is the ratio of the heat transfer ratewith fluid flow to the heat transfer rate in the absence of fluid flowNu=Q_(flow)/Q_(no-flow). The magnitude of the enhancement in heattransfer by fluid flow can be estimated by the Nusselt number. Forconvective heat transfer between blood and the surface of the heattransfer element, Nusselt numbers of 30 to 80 have been found to beappropriate for selective cooling applications of various organs in thehuman body. Nusselt numbers are generally dependent on several othernumbers: the Reynolds number, the Womersley number, and the Prandtlnumber. Enhancement of the heat transfer rate in embodiments of thepresent invention may be described by a Nusselt number of between 10 and50.

FIG. 10 is a schematic representation of the invention being used tocool the brain of a patient. The selective organ hypothermia apparatusshown in FIG. 10 includes a working fluid supply 10, preferablysupplying a chilled liquid such as water, alcohol or a halogenatedhydrocarbon, a supply catheter 12 and the heat transfer element 14. Thesupply catheter 12 has a coaxial construction. An inner coaxial lumenwithin the supply catheter 12 receives coolant from the working fluidsupply 10. The coolant travels the length of the supply catheter 12 tothe heat transfer element 14 which serves as the cooling tip of thecatheter. At the distal end of the heat transfer element 14, the coolantexits the insulated interior lumen and traverses the length of the heattransfer element 14 in order to decrease the temperature of the heattransfer element 14. The coolant then traverses an outer lumen of thesupply catheter 12 so that it may be disposed of or recirculated. Thesupply catheter 12 is a flexible catheter having a diameter sufficientlysmall to allow its distal end to be inserted percutaneously into anaccessible artery such as the femoral artery of a patient as shown inFIG. 10. The supply catheter 12 is sufficiently long to allow the heattransfer element 14 at the distal end of the supply catheter 12 to bepassed through the vascular system of the patient and placed in theinternal carotid artery or other small artery. The method of insertingthe catheter into the patient and routing the heat transfer element 14into a selected artery is well known in the art.

The working fluid supply 10 would preferably include a chiller and apump. The pump can be a gear pump, a peristaltic pump, or some othertype. A gear pump may be preferable, since the attainable pressure witha gear pump may be higher, and the relationship of the volume flow rateto the pump speed may be more linear with a gear pump than with otherpumps. Two types of gear pumps which would be suitable, among others,are radial spur gear pumps and helical tooth gear pumps. A helical toothgear pump may provide higher pressure and more constant flow rate than aspur gear pump. The ability to achieve high pressures may be important,as the cooling fluid is required to pass through a fairly narrowcatheter at a certain, dependable, rate. For the same reason, theviscosity of the fluid, at low temperatures, should be appropriatelylow.

Although the working fluid supply 10 is shown as an exemplary coolingdevice, other devices and working fluids may be used. For example, inorder to provide cooling, freon, perfluorocarbon, water, or saline maybe used, as well as other such coolants.

The heat transfer element can absorb or provide over 75 Watts of heat tothe blood stream and may absorb or provide as much as 100 Watts, 150Watts, 170 Watts or more. For example, a heat transfer element with adiameter of 4 mm and a length of approximately 10 cm using ordinarysaline solution chilled so that the surface temperature of the heattransfer element is approximately 5° C. and pressurized at 2 atmospherescan absorb about 100 Watts of energy from the bloodstream. Smallergeometry heat transfer elements may be developed for use with smallerorgans which provide 60 Watts, 50 Watts, 25 Watts or less of heattransfer.

FIG. 11 is a perspective view of a third embodiment of a heat transferelement 70 according to the present invention. The heat transfer element70 is comprised of a series of elongated, articulated segments ormodules 72. A first elongated heat transfer segment 72 is located at theproximal end of the heat transfer element 70. The segment 72 may be asmooth right circular cylinder, as addressed in FIG. 3C, or it canincorporate a turbulence-inducing or mixing-inducing exterior surface.The turbulence-inducing or mixing-inducing exterior surface shown on thesegment 72 in FIG. 11 comprises a plurality of parallel longitudinalridges 74 with parallel longitudinal grooves 76 therebetween. One, two,three, or more parallel longitudinal ridges 74 could be used withoutdeparting from the spirit of the present invention. In the embodimentwhere they are used, the longitudinal ridges 74 and the longitudinalgrooves 76 of the heat transfer segment 72 are aligned parallel with theaxis of the first heat transfer segment 72.

The first heat transfer segment 72 is coupled to a second elongated heattransfer segment 72 by a first flexible section such as a bellowssection 78, which provides flexibility and compressibility.Alternatively, the flexible section may be a simple flexible tube, verysimilar to a smooth heat transfer segment as addressed in FIG. 3C, butflexible. The second heat transfer segment 72 also comprises a pluralityof parallel longitudinal ridges 74 with parallel longitudinal grooves 76therebetween. The longitudinal ridges 74 and the longitudinal grooves 76of the second heat transfer segment 72 are aligned parallel with theaxis of the second heat transfer segment 72. The second heat transfersegment 72 is coupled to a third elongated heat transfer segment 72 by asecond flexible section such as a bellows section 78 or a flexible tube.The third heat transfer segment 72 also comprises a plurality ofparallel longitudinal ridges 74 with parallel longitudinal grooves 76therebetween. The longitudinal ridges 74 and the longitudinal grooves 76of the third heat transfer segment 72 are aligned parallel with the axisof the third heat transfer segment 72. Further, in this embodiment,adjacent heat transfer segments 72 of the heat transfer element 70 havetheir longitudinal ridges 74 aligned with each other, and theirlongitudinal grooves 76 aligned with each other.

In addition, the rounded contours of the ridges 74 also allow the heattransfer element 70 to maintain a relatively atraumatic profile, therebyminimizing the possibility of damage to the blood vessel wall. A heattransfer element 70 according to the present invention may be comprisedof two, three, or more heat transfer segments 72.

The bellows sections 78 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidwhich is cycled through the heat transfer element 70. The structure ofthe bellows sections 78 allows them to bend, extend and compress, whichincreases the flexibility of the heat transfer element 70 so that it ismore readily able to navigate through blood vessels. The bellowssections 78 also provide for axial compression of the heat transferelement 70, which can limit the trauma when the distal end of the heattransfer element 70 abuts a blood vessel wall. The bellows sections 78are also able to tolerate cryogenic temperatures without a loss ofperformance, facilitating use of the heat transfer element in lowtemperature ablation of tissue.

FIG. 12 is a perspective view of a fourth embodiment of a heat transferelement 80 according to the present invention. The heat transfer element80 is comprised of a series of elongated, articulated segments ormodules 82. A first elongated heat transfer segment 82 is located at theproximal end of the heat transfer element 80. A turbulence-inducing ormixing-inducing exterior surface of the segment 82 comprises a pluralityof parallel longitudinal ridges 84 with parallel longitudinal grooves 86therebetween. One, two, three, or more parallel longitudinal ridges 84could be used without departing from the spirit of the presentinvention. In this embodiment, the longitudinal ridges 84 and thelongitudinal grooves 86 of the heat transfer segment 82 are alignedparallel with the axis of the first heat transfer segment 82.

The first heat transfer segment 82 is coupled to a second elongated heattransfer segment 82 by a first flexible section such as a bellowssection 88, which provides flexibility and compressibility.Alternatively, the flexible section may be a simple flexible tube, verysimilar to a smooth heat transfer segment as shown in FIG. 3C, butflexible. The second heat transfer segment 82 also comprises a pluralityof parallel longitudinal ridges 84 with parallel longitudinal grooves 86therebetween. The longitudinal ridges 84 and the longitudinal grooves 86of the second heat transfer segment 82 are aligned parallel with theaxis of the second heat transfer segment 82. The second heat transfersegment 82 is coupled to a third elongated heat transfer segment 82 by asecond flexible section such as a bellows section 88 or a flexible tube.The third heat transfer segment 82 also comprises a plurality ofparallel longitudinal ridges 84 with parallel longitudinal grooves 86therebetween. The longitudinal ridges 84 and the longitudinal grooves 86of the third heat transfer segment 82 are aligned parallel with the axisof the third heat transfer segment 82. Further, in this embodiment,adjacent heat transfer segments 82 of the heat transfer element 80 havetheir longitudinal ridges 84 angularly offset from each other, and theirlongitudinal grooves 86 angularly offset from each other. Offsetting ofthe longitudinal ridges 84 and the longitudinal grooves 86 from eachother on adjacent segments 82 promotes turbulence or mixing in bloodflowing past the exterior of the heat transfer element 80.

FIG. 13 is a transverse section view of a heat transfer segment 90,illustrative of segments 72, 82 of heat transfer elements 70, 80 shownin FIG. 11 and FIG. 12. The coaxial construction of the heat transfersegment 90 is clearly shown. The inner coaxial lumen 92 is defined bythe insulating coaxial tube 93. The outer lumen 98 is defined by theexterior surface of the insulating coaxial tube 93 and the interiorsurface 99 of the heat transfer segment 90. In addition, parallellongitudinal ridges 94 and parallel longitudinal grooves 96 may be seenin FIG. 13. The longitudinal ridges 94 and the longitudinal grooves 96may have a relatively rectangular cross-section, as shown in FIG. 13, orthey may be more triangular in cross-section, as shown in FIGS. 11 and12. The longitudinal ridges 94 and the longitudinal grooves 96 may beformed only on the exterior surface of the segment 90, with acylindrical interior surface 99. Alternatively, correspondinglongitudinal ridges and grooves may be formed on the interior surface 99as shown, to promote turbulence or mixing in the working fluid. AlthoughFIG. 13 shows six ridges and six grooves, the number of ridges andgrooves may vary. Where a smooth exterior surface is desired, the outertube of the heat transfer segment 90 could have smooth outer and innersurfaces, like the inner tube 93. Alternatively, the outer tube of theheat transfer segment 90 could have a smooth outer surface and a ridgedinner surface like the interior surface 99 shown in FIG. 13.

The practice of the invention is illustrated in the followingnon-limiting example.

Exemplary Procedure

1. The patient is initially assessed, resuscitated, and stabilized.

2. The procedure is carried out in an angiography suite or surgicalsuite equipped with fluoroscopy.

3. Because the catheter is placed into the common carotid artery, it isimportant to determine the presence of stenotic atheromatous lesions. Acarotid duplex (doppler/ultrasound) scan can quickly and non-invasivelymake this determinations. The ideal location for placement of thecatheter is in the left carotid so this may be scanned first. If diseaseis present, then the right carotid artery can be assessed. This test canbe used to detect the presence of proximal common carotid lesions byobserving the slope of the systolic upstroke and the shape of thepulsation. Although these lesions are rare, they could inhibit theplacement of the catheter. Examination of the peak blood flow velocitiesin the internal carotid can determine the presence of internal carotidartery lesions. Although the catheter is placed proximally to suchlesions, the catheter may exacerbate the compromised blood flow createdby these lesions. Peak systolic velocities greater that 130 cm/sec andpeak diastolic velocities >100 cm/sec in the internal indicate thepresence of at least 70% stenosis. Stenosis of 70% or more may warrantthe placement of a stent to open up the internal artery diameter.

4. The ultrasound can also be used to determine the vessel diameter andthe blood flow and the catheter with the appropriately sized heattransfer element could be selected.

5. After assessment of the arteries, the patients inguinal region issterilely prepped and infiltrated with lidocaine.

6. The femoral artery is cannulated and a guide wire may be inserted tothe desired carotid artery. Placement of the guide wire is confirmedwith fluoroscopy.

7. An angiographic catheter can be fed over the wire and contrast mediainjected into the artery to further to assess the anatomy of thecarotid.

8. Alternatively, the femoral artery is cannulated and a 10-12.5 french(f) introducer sheath is placed.

9. A guide catheter is placed into the desired common carotid artery. Ifa guiding catheter is placed, it can be used to deliver contrast mediadirectly to further assess carotid anatomy.

10. A 10 f-12 f (3.3-4.0 mm) (approximate) cooling catheter issubsequently filled with saline and all air bubbles are removed.

11. The cooling catheter is placed into the carotid artery via theguiding catheter or over the guidewire. Placement is confirmed withfluoroscopy.

12. Alternatively, the cooling catheter tip is shaped (angled or curvedapproximately 45 degrees), and the cooling catheter shaft has sufficientpushability and torqueability to be placed in the carotid without theaid of a guide wire or guide catheter.

13. The cooling catheter is connected to a pump circuit also filled withsaline and free from air bubbles. The pump circuit has a heat exchangesection that is immersed into a water bath and tubing that is connectedto a peristaltic pump. The water bath is chilled to approximately 0° C.

14. Cooling is initiated by starting the pump mechanism. The salinewithin the cooling catheter is circulated at 5 cc/sec. The salinetravels through the heat exchanger in the chilled water bath and iscooled to approximately 1° C.

15. It subsequently enters the cooling catheter where it is delivered tothe heat transfer element. The saline is warmed to approximately 5-7° C.as it travels along the inner lumen of the catheter shaft to the end ofthe heat transfer element.

16. The saline then flows back through the heat transfer element incontact with the inner metallic surface. The saline is further warmed inthe heat transfer element to 12-15° C., and in the process, heat isabsorbed from the blood, cooling the blood to 30° to 32° C.

17. The chilled blood then goes on to chill the brain. It is estimatedthat 15-30 minutes will be required to cool the brain to 30 to 32° C.

18. The warmed saline travels back down the outer lumen of the cathetershaft and back to the chilled water bath where it is cooled to 1° C.

19. The pressure drops along the length of the circuit are estimated tobe 2-3 atm.

20. The cooling can be adjusted by increasing or decreasing the flowrate of the saline. Monitoring of the temperature drop of the salinealong the heat transfer element will allow the flow to be adjusted tomaintain the desired cooling effect.

21. The catheter is left in place to provide cooling for 12 to 24 hours.

22. If desired, warm saline can be circulated to promote warming of thebrain at the end of the therapeutic cooling period.

The invention herein disclosed is capable of obtaining the statedobjects, but no limitations are intended other than as described in theappended claims.

1. A heat transfer device for low temperature ablation of tissue,comprising: first and second elongated segments, one of said first orsecond elongated segments providing a closed end of said heat transferdevice; a bellows structure connecting said first and second elongatedsegments, said bellows structure being less thermally conductive thansaid first and second elongated segments by virtue of inherent fluidstagnation on the surface of said bellows structure; and a tubularconduit disposed within and extending substantially through said firstand second elongated segments, said conduit having an inner lumen fortransporting a working fluid to a distal end of said one of said firstor second elongated segments providing a closed end of said heattransfer device.
 2. The device recited in claim 1, further comprising asmooth outer surface on at least one of said first and second elongatedsegments.
 3. The device recited in claim 1, wherein said first andsecond elongated segments are formed from highly conductive material. 4.The device recited in claim 1, further comprising: a coaxial supplycatheter having an inner catheter lumen coupled to said inner lumen ofsaid tubular conduit; and a working fluid supply configured to dispensesaid working fluid and having an output coupled to said inner catheterlumen.
 5. The device recited in claim 4, wherein said working fluidsupply is adapted to dispense a perfluorocarbon working fluid.
 6. Thedevice recited in claim 4, wherein said working fluid supply is adaptedto produce a pressurized said working fluid at a temperature less thanabout 0 degrees C.
 7. The device recited in claim 1, further comprising:at least one additional elongated segment; and at least one additionalbellows structure connecting said at least one additional elongatedsegment to one of said first and second elongated segments.
 8. Thedevice recited in claim 1, wherein said bellows structure is lessthermally conductive than said first and second elongated segments byvirtue of fluid stagnation on the outer surface of said bellowsstructure.
 9. The device recited in claim 1, wherein said bellowsstructure is less thermally conductive than said first and secondelongated segments by virtue of fluid stagnation on the inner surface ofsaid bellows structure.
 10. The device recited in claim 1, wherein saidbellows structure is less thermally conductive than said first andsecond elongated segments by virtue of fluid stagnation on both theinner and outer surfaces of said bellows structure.